Survival rates for children with acute lymphoblastic leukemia (ALL) have been improved dramatically in the last decade. A major contributing feature of successful therapy was the introduction of central nervous system (CNS) prophylaxis (intrathecal methotrexate and cranial irradiation). However, many long-term survivors have now been found to exhibit cognitive deficits. This impairment is generally attributed to damage sustained by the developing nervous system in the course of treatment. The child's age at the time of treatment is apparently a critical factor. Existing studies suggest that children who are younger when treated exhibit more severe deficits. The proposed study is a detailed examination of the relationship of CNS impairment to the age at which CNS prophylaxis is administered. Specifically, we shall determine how the severity and nature of impairment are related to treatment age, the role of time elapsed since treatment, and the role of experimental factors related to life-threatening illness in childhood. A retrospective study is planned in which approximately 100 long-term survivors will receive a detailed neurological and neuropsychological evaluation. This study will provide a detailed assessment of the sequelae of CNS prophylaxis. Its findings will be of considerable value in evaluating the relative risks and benefits of treatment as well as in providing adequate counseling and treatment for the increasing number of long-term survivors who are now presenting with significant cognitive and behavioral difficulties. In addition, the study provides a unique opportunity to gain insight into normal and abnormal processes of human CNS development in the early years of life.